Last week the National Breast Cancer Coalition (NBCC) held its annual summit. The meeting drew over 600 women to its opening rally in a Crystal City ballroom on Saturday, along with students who participated in sessions for Emerging Leaders, and a few men who joined in lectures and panels, and lobbied on Tuesday on Capitol Hill.

The opening rally, organized in the style of a political convention, was lively. When I entered, participants – or “activists,” as they might be called – were rocking to Three Dog Night’s Joy to the World. Attendees congregated by state and region. Most wore festive garments and signs over black tee shirts carrying the Deadline logo: women from Maine wore floppy red lobster hats; a contingent from Pennsylvania held brightly-decorated kite-posters; a group from Oregon played kazoos (to We’re Not Gonna Take It) and supported multicolored umbrellas over their heads; members of the CBCC lifted Rosie the Riveter boards proclaiming: “We Can Do It!” Each region offered a progress report. In videos, these demonstrated a mix of activism (“waving breast cancer goodbye” on a Rhode Island beach) and seriousness (scientist in a lab, explaining why the research matters).

Fun aside – the meeting’s mood was overwhelmingly serious. Each day’s session opened with a moment of silence to recall women who have died from breast cancer. There were plenary lectures, and smaller educational meetings on topics like “A Critical Review of New Therapies for Metastatic Breast Cancer,” “Estrogen Exposure throughout the Life Cycle,” “Nuts and Bolts of Congress,” “and “The Environment and Breast Cancer.” Many of the women there have metastatic cancer, or had cancer. I had lunch one day with a woman whose early-stage cancer came back after 15 years. Many of the college-age people attending have moms with advanced disease or who died from that. There were young people who’d had breast cancer – some under 30 years old. The few men I spoke with were affected by their wives and mothers’ illnesses. You couldn’t walk a few feet without hearing a sad tale, or seeing the outcome of loss, in motivating people to take action.

In her remarks, Fran Visco, the NBCC Founder and leader, reminded the group that breast cancer remains a leading cause of cancer deaths. Each day, on average, 110 women die in the U.S. from breast cancer. That’s the equivalent of a woman dying every 14 minutes from the disease, she explained. “This should not be considered success, or even meaningful progress.”

“We need to take a less comfortable approach,” she said. “The system rewards safe ideas. We need to take risks.” She spoke of the Artemis project, an NBCC-supported research program to develop a preventive breast cancer vaccine. “There’s a moral imperative to do these trials,” she said. “We’ll get scientists to form new collaborations, to change their focus not on the next grant, or publication, but on the real goal, which is saving patients’ lives.”

In the 20 years since NBCC was founded there’s been progress, she said. “But we’re nowhere near close enough.” She referred to Dr. Jonas Salk, whose polio vaccine came through after just seven years in the lab, and – as did others at the same meeting – to JFK’s 1961 promise to put a man on the moon. That seemingly impossible mission got done in less than nine years. The idea of the Accelerating the End of Breast Cancer Act is to leverage our nation’s prior investment in biotechnology, and to use that work – including much research already done – to end to breast cancer and stop metastases. Visco hopes to deliver a petition to the President on inauguration day in January, 2013.

Through the meeting, I gained a better sense of the organization and Deadline’s purpose. In the words of Senator Kirsten Gillebrand, who met with a delegation from New York on Tuesday: “It creates an urgency about the issue.”

Breast cancer is not one disease. We’ve understood this for decades. Still, and with few exceptions, knowledge of BC genetics – information on tumor-driving DNA mutations within the malignant cells – has been lacking. Most patients today get essentially primitive treatments like surgical hacking, or carving, traditional chemotherapy and radiation. Some doctors consider hormone therapy as targeted, and thereby modern and less toxic. I don’t.

Until there’s a way to prevent BC, we need better ways to treat it. Which is why, upon reading the new paper in Nature on genetic patterns in breast cancer, I stayed up late, genuinely excited. As in thrilled, optimistic..The research defined 10 molecular BC subgroups. The distinct mutations and gene expression patterns confirm and suggest new targets for future, better therapy.

The work is an exquisite application of science in medicine. Nature lists 31 individuals and one multinational research group, METABRIC (Molecular Taxonomy of Breast Cancer International Consortium), as authors. The two correspondents, Drs. Carlos Caldas and Samuel Aparicio, are based at the University of Cambridge, in England, and the University of British Columbia in Vancouver, Canada. Given the vastness of the supporting data, such a roster seems appropriate, needed. The paper, strangely and for all its worth, didn’t get much press –

Just to keep this in perspective – we’re talking about human breast cancer. No mice.

The researchers examined nearly 2000 BC specimens for genetic aberrations, in 2 parts. First, they looked at inherited and acquired mutations in DNA extracted from tumors and, when available, from nearby, normal cells, in 997 cancer specimens – the “discovery set.” They checked to see how the genetic changes (SNPs, CNAs and/or CNVs) correlated with gene expression “landscapes” by probing for nearly 29,000 RNAs. They found that both inherited and acquired mutations can influence BC gene expression. Some effects of “driver” mutations take place on distant chromosomal elements, in what’s called a trans effect; others happen nearby (cis).

Next, they honed in on 45 regions of DNA associated with outlying gene expression. This led the investigators to discover putative cancer-causing mutations (accessible in supplementary Tables 22-24, available here). The list includes genes that someone like me, who’s been out of the research field for 10 years, might recall – PTEN, MYC, CDK3 and -4, and others. They discovered that 3 genes, PPP2R2A, MTAP and MAP2K4 are deleted in some BC cases and may be causative. In particular, they suggest that loss of PPP2R2A may contribute to luminal B breast cancer pathology. They find deletion of MAP2K4 in ER positive tumors, indicative of a possible tumor suppressor function for this gene in BC.

Curtis, et al. in "Nature": April 2012

The investigators looked for genetic “hotspots.” They show these in Manhattan plots, among other cool graphs and hard figures, on abnormal gene copy numbers (CNAs) linked to big changes in gene expression. Of interest to tumor immunologists (and everyone else, surely!), they located two regions in the T-cell receptor genes that might relate to immune responses in BC. They delineated a part of chromosome 5, where deletions in basal-like tumors marked for changes in cell cycle, DNA repair and cell death-related genes. And more –

Cluster Analysis (abstracted), Wikipedia

Heading toward the clinic, almost there…

They performed integrative cluster analyses and defined 10 distinct molecular BC subtypes. The new categories of the disease, memorably labeled “IntClust 1-10,” cross older pathology classifications (open-access: Supplementary Figure 31) and, it turns out, offer prognostic information based on long-term Kaplan-Meier analyses (Figure 5A in the paper: Supplementary Fig 34 and 35). Of note, here, and a bit scary for readers like me, is identification of an ER-positive group, “IntClust 2” with 11q13/14 mutations. This BC genotype appears to carry a much lesser prognosis than most ER-positive cases.

Finally, in what’s tantamount to a 2nd report, the researchers probed a “validation set” of 995 additional BC specimens. In a partially-shortened method, they checked to see if the same 10 molecular subtypes would emerge upon a clustering analysis of paired DNA mutations with expression profiles. What’s more, the prognostic (survival) information held up in the confirmatory evaluation. Based on the mutations and gene expression patterns in each subgroup, there are implications for therapy. Wow!

I won’t review the features of each type here for several reasons. These are preliminary findings, in the sense that it’s a new report, albeit a model of what’s a non-incremental published set of observations and analysis; it’s early for patients – but not for investigators – to act on these findings. (Hopefully, this will not be the case in 2015, or sooner, preferably, for testing some pertinent drugs in at least a subset of the subgroups identified.) Also, some of the methods these authors used came out in the past decade, after I stopped doing research. It would be hard for most doctors to fully appreciate the nuances, strengths and weaknesses of the study.

Most readers can’t know how skeptical I was in the 1990s, when grant reviewers at the NCI seemed to believe that genetic info would be the cure-all for most and possibly all cancers. I don’t think that’s true, nor due most people involved with the Human Genome Project, anymore. The Cancer Genome Atlas and Project should help in this regard, but they’re young projects, larger in scope than this work, and don’t necessarily integrate DNA changes with gene expression as do the investigators in this report. What’s clear, now, is that some cancers do respond, dramatically, to drugs that target specific mutations. Recently-incurable malignancies, like advanced melanoma and GI stromal tumors, can be treated now with pills, often with terrific responses.

Last night I wondered if, in a few years, some breast cancers might be treated without surgery. If we could do a biopsy, check for the molecular subtype, and give patients the right BC tablets. Maybe we’d just give just a tad of chemo, later, to “mop up” any few remaining or residual or resistant cells. The primary chemotherapy might be a cocktail of drugs, by mouth. It might be like treating hepatitis C, or tuberculosis or AIDS. (Not that any of those are so easy.) But there’d be no lost breasts, no reconstruction, no lymphedema. Can you imagine?

Even if just 1 or 2 of these investigators’ subgroups pans out and leads to effective, Gleevec-like drugs for breast cancer, that would be a dream. This can’t happen soon enough.

With innovative trial strategies like I-SPY, it’s possible that for patients with particular molecular subgroups could be directed to trials of small drugs targeting some of the pathways implicated already. The pace of clinical trials has been impossibly slow in this disease. We (and by this I mean pharmaceutical companies, and oncologists who run clinical trials, and maybe some of the BC agencies with funds to spend) should be thinking fast, way ahead of this post –

And given that this is a blog, and not an ordinary medical publication or newspaper, I might say this: thank you, authors, for your work.

The idea is for women to take photos of their breasts, send them in, and raise awareness about the importance of healthy breasts.

You can look and “like” Boobstagram on Facebook. Over 20,000 have registered their appreciation for the site, so far. The timeline reveals that Boobstagram opened a FB account last November and first uploaded images late in February. The About page starts with this message: Send us your boobs at boobstagram@… When I visited yesterday, at around 7PM EST, over 9,000 people were “talking” about Boobstagram on FB. Boobstagram’s Twitter following is on the small side, relatively, perhaps because it’s an image-oriented source of awareness.

Instagr.am, for those readers who use Blackberries or might be otherwise out-of-the-loop, is a phone app that lets you take and share photos in a flash. Coincidentally, Facebook recently purchased Instagram for $300 in cash, plus.

On its main website, the company’s tag line is translated into English: “Showing your boobs on the web is good, showing them to your doctor is better.” The explanation continues:

…The fight against cancer is long-standing…We cannot all become doctors or surgeons. But we can all take part in prevention, for ourselves, for our friends and family and for others. But how?

…How to avoid the pitfall of moralism ? How to build a popular communication matching with the up-to-date scientific knowledge ? And how to create a rather fun prevention campaign when most campaigns use fear ?<sic>

Capiche? Not sure I do. (Please forgive me if I mix languages and messages, for the moment.) This topic’s ripe, pre-blended. And sort-of fun, as things go here.

Fact is – once I’d narrowed the post topic selections to either Boobstagram or a recent report on 10 distinct genetic breast cancer variants, I chose Boobstagram. The Nature paper is very important work. Fox News called it a landmark study, correctly from what I’ve read elsewhere. I should read up on the new genotypes, and learn how those relate to old-fashioned BC subtypes, and the prognosis and potential for targeted therapies directed to each. And so should, I suppose, breast cancer patients and their loved ones who wish to make informed decisions. Practicing oncologists should know all about that paper by now, digested it entirely.

Business Insider covered Boobstagram, but overall there’s not been a whole lot of attention in the U.S. HuffPo U.K. was on it, but not here, where I might post if I choose. I’m not sure if I will, or should –

This company, founded by two men, seems to be having some fun with cancer, women’s breasts and phones. Is it exploitative? I’m not sure whether to laugh, cry, or blow it off as boys behaving badly. Or girls behaving badly. Or both, together, normally.

It’s sexist, yes – but so’s an ordinary half-time show during a football game, or a pair of 4-inch heels. Besides, many tolerate infantilizing and commercializing events in the context of BC awareness, as Gayle Sulik points out. Those campaigns – some tawdry, some tasteful, and usually bright pink – rake in money for research and patient care. Is Boobstagram so different? Strictly off-limits?

Seriously, what if the website brought in 180 million Euros through ads next year, and the company founders gave it all to the IARC and a few really solid cancer research agencies? Maybe next year their American friends will open a similar platform to raise money for the strapped NCI.

Are we too uptight? Or is the problem simply that the French website lacks meaningful relevance to any cancer cause?

The almost-obvious, pat and probably correct answer, would be to call out Boobstagram for what it’s worth: a farce. There’s no hint that this company has a specific plan or funds to support cancer research or help patients in any meaningful way. I can’t support it. But maybe – and this is a stretch – in the long term cultivating love, or admiration… of women’s breasts raises their value, and reminds us of the tragedy that is breast cancer.

CER is a big deal in medicine now. Dry as it is, it’s an investigative method that any doctor or health care maven, politician contemplating reform or, maybe, a patient would want to know. The gist of CER is that it exploits large data sets – like SEER data or Medicare billing records – to examine outcomes in huge numbers of people who’ve had one or another intervention. An advantage of CER is that results are more likely generalizable, i.e. applicable in the “real world.” A long-standing criticism of randomized trials – held by most doctors, and the FDA, as the gold standard for establishing efficacy of a drug or procedure – is that patients in research studies tend to get better, or at least more meticulous, clinical care.

The JAMA program began with an intro by Dr. Phil Fontanarosa, a senior editor and author of an editorial on CER, followed by 4 presentations. The subjects were, on paper, shockingly dull: on carboplatin and paclitaxel w/ and w/out bevacizumab (Avastin) in older patients with lung cancer; on survival in adults who receive helicopter vs. ground-based EMS service after major trauma; a comparison of side effects and mortality after prostate cancer treatment by 1 of 3 forms of radiation (conformal, IMRT, or proton therapy); and – to cap it off – a presentation on PCORI‘s priorities and research agenda.

I learned from each speaker. They brought life to the topics! Seriously, and the scene made me realize the value of meeting and hearing from the researchers, directly, in person. But, NTW, on ML today we’ll skip over the oncologist’s detailed report to the second story:

Dr. Adil Haider, a trauma surgeon at Johns Hopkins, spoke on helicopter-mediated saves of trauma patients. Totally cool stuff; I’d rate his talk “exotic” – this was as far removed from the kind of work I did on molecular receptors in cancer cells as I’ve ever heard at a medical or journalism meeting of any sort –

Haider indulged the audience, and grabbed my attention, with a bit of history: HEMS, which stands for helicopter-EMS, goes back to the Korean War, like in M*A*S*H. The real-life surgeon-speaker at the JAMA news briefing played a music-replete video showing a person hit by a car and rescued by helicopter. While he and other trauma surgeons see value in HEMS, it’s costly and not necessarily better than GEMS (Ground-EMS). Helicopters tend to draw top nurses, and they deliver patients to Level I or II trauma centers, he said, all of which may favor survival and other, better outcomes after serious injury. Accidents happen; previous studies have questioned the helicopters’ benefit.

The problem is, there’s been no solid randomized trial of HEMS vs. GEMS, nor could there be. (Who’d want to get the slow pick-up with a lesser crew to a local trauma center?) So these investigators did a retrospective cohort study to see what happens when trauma victims 15 years and older are delivered by HEMS or GEMS. They used data from the National Trauma Data Bank (NTDB), which includes nearly 62,000 patients transported by helicopter and over 161,000 patients transported by ground between 2007 and 2009. They selected patients with ISS (Injury severity scores) above 15. They used a “clustering” method to control for differences among trauma centers, and otherwise adjusted for degrees of injury and other confounding variables.

“It’s interesting,” Haider said. “If you look at the unadjusted mortality, the HEMS patients do worse.” But when you control for ISS, you get a 16% increase in odds of survival if you’re taken by helicopter to a Level I trauma center. He referred to Table 3 in the paper. This, indeed, shows a big difference between the “raw” and adjusted data.

When you first look, across the board, you’ll see that actually more patients transported by helicopter, in terms of just the raw percentages, actually die.” – Dr. Samuel Galvagno (DO, PhD), the study’s first author.

The video immediately cuts to the senior author, Haider, who continues:

But when you do an analysis controlling for how severely these patients were injured, the chance of survival improves by about 30 percent, for those patients who are brought by helicopter…

—

Big picture:

What’s clear is that how investigators adjust or manipulate or clarify or frame or present data – you choose the verb – yields differing results. This capability doesn’t just pertain to data on trauma and helicopters. In many Big Data situations, researchers can cut information to impress whatever point they choose.

The report offers a case study of how researchers can use elaborate statistical methods to support a clinical decision in a way that few doctors who read the results are in a position to grasp, to know if the conclusions are valid, or not.

A concluding note –

I appreciated the time allotted for Q&A after the first 3 research presentations. There’s been recent, legitimate questioning of the value of medical conferences. This week’s session, sponsored by JAMA, reinforced to me the value of meeting study authors in person, and having the opportunity to question them about their findings. This is crucial, I know this from my prior experience in cancer research, when I didn’t ask enough hard questions of some colleagues, in public. For the future, at places like TEDMED – where I’ve heard there was no attempt to allow for Q&A – the audience’s concerns can reveal problems in theories, published data and, constructively, help researchers fill in those gaps, ultimately to bring better-quality information, from any sort of study, to light.

This post is probably a bad idea. But I’ve been pondering it for two days now, since the room around me starting spinning. And I wish I were Jack Kerouac now, so that it wouldn’t matter so much if my thoughts are clear but that I tapped them out. Rat tat tat. Or Frank Sinatra with a cold. You’d want to know either of those guys, in detail. Up-close, loud, even breathing on you. You’d hire ‘em. Because even when they’re down, they’re good. Handsome. Cool, slick, unforgettable. Illness doesn’t capture them, or define them.

Two days ago I was feeling great. I went to the National Press Club for the first time, and was excited about some presentations I heard there, about which I took careful notes and intend, eventually, to share with some commentary. It was a sunny day, and I bought some groceries, planning a bunch of posts and to finish a freelance piece. In the evening I had dinner with my husband, and it seemed like my life was on track.

The rash was the first thing. Just some red, itchy bumps on the back of my neck. And then fatigue. Not just a little tired, but like I couldn’t write a sentence. And since then I’ve been in the center of a kaleidoscope, everything moving clockwise around my head. It’s not bright purple or hot pink and blue and stained glass-green kinds of colors circling, but the drab objects in the bedroom: the lamp, the shadow cast by the top of the door, the rows of light through the blinds, the brown and beige sheets, the back cover of last month’s Atlantic and my reading glasses on the nightstand, the gray bowl I’ve placed at hand, just in case I barf again. Walking is tricky. I’m dehydrated and weak, and my vision’s blurred.

This is not a pretty scene, if you could see it. And that’s the thing. The point.

Because in my experience, which is not trivial, people on both sides of illness – professionals and people you just know – are drawn to healthy people. A broken arm, a low-stage breast cancer that’s treated and done with, a bout of pneumonia – these are things that a career can afford, an editor can handle, friends can be supportive. But when you have one thing, and then another, and then another, it gets scary, it weighs you down. Just when you start feeling OK, and confident, something happens and you’re back, as a patient.

Today, in the apartment on this spring day, with fever and fatigue, I’ve got no choice. I am not a consumer now. Not even close. That is my role, maybe, when I go to the dentist and decline having x-rays or my teeth whitened. No choice, except if I go to a hospital, to have a bunch of blood drawn and my husband would fill in the forms before the doctors who don’t know me in this city inform me I’ve got a viral infection, and labrynthitis as I’ve had a dozen times before, all of a sudden, disabling. Nothing to do but rest and hydrate. And wish I’d gotten some other work done, but I couldn’t.

I’ve got to go with it, my health or illness, be that as it is. No careful critiques of comparative effectiveness research today. No reading about the Choosing Wisely guidelines. No post on Dengue, as I’d planned for yesterday. Like many people with illnesses – and many with far more serious conditions – I’m disappointed. Maybe because I was sick as a child and missed half of tenth grade, I have trouble accepting these kinds of disruptions. Illness represents a loss of control, besides all the physical aspects.

I might try to watch TV, but more likely I’ll just fall sleep again. That happened yesterday. And for those of you health IT or gadget guys reading, who talk about smart phones and how useful they are for patients seeking info, or maybe even checking vitals, I’ll say this: I’m just glad I’ve got such a device, simply that I can call for help, that I can be in touch, call my doctor and family. That makes being sick less scary.

This is a drag of a post, but it’s real. No point in blogging if I don’t say it like it is, what I am. If nothing else, this proves I’m alive. So there!

This past week I read several attitude-altering articles about breast cancer.

Kathy Rich, as featured in ‘O’ Magazine

The first lesson, if I might call it that – in the way an oncologist can learn from variations in her patients’ pathology and clinical outcomes – comes from the case of Katherine Russell Rich, who died last week at the age of 56. As reported by Katherine O’Brien in the I Hate Breast Cancer Blog, Rich lived with metastatic BC (MBC) for 18 years. That’s phenomenal, was my first reaction to this news. The prognosis for MBC is said to be around 3 years, and Rich lived for 18 years beyond her tumor’s recurrence with stage IV disease.

As sad and unsatisfactory as this outcome may seem, and it is, Rich’s story offers hope for life beyond the 3 or 4 or 5 years some women with MBC pray, “ask” or otherwise bargain for, fingers-crossed…

As she detailed in an O article, Rich’s initial diagnosis came when she was 32 years old, in 1988. The Times, in an obituary, tells of her lumpectomy, chemo and radiation. In 1993 her cancer came back in bones including her spine. She had a bone marrow transplant, but the disease progressed. Ultimately, she coursed through various and some archaic hormone treatments.

Along the way, she lost or quit a job in publishing, or both, and traveled to India, and authored two books. In a 2010 first-person story about her case, she told of updating her status – of being alive – at Breastcancer.org each year. She wrote:

…I tell the women how deeply I believe there’s no such thing as false hope: all hope is valid, even for people like us, even when hope would no longer appear to be sensible.

Life itself isn’t sensible, I say. No one can say with ultimate authority what will happen — with cancer, with a job that appears shaky, with all reversed fortunes — so you may as well seize all glimmers that appear.

My take, as an oncologist and former clinician, is that patients sometimes surprise you. Hard to know which woman will respond to a non-targeted treatment, or even a drug like an estrogen modulator, without trying. And I wonder – and this is speculative, but maybe, likely, the two together – doctor and patient – worked together to see what worked in Rich’s case over nearly 2 decades, and what didn’t work.

A Bell Curve

If a drug helps, keep it going; if it hurts, stop. There are so many algorithms in medicine, and molecular tools, but maybe the bottom line is how the, one, your patient is doing.

Which leads me to another post, by Dr. David Gorski, a breast cancer surgeon and researcher who blogs as Orac – what once was imagined as a fabulously capable information processor, at Respectful Insolence. He describes how tough it can be to define, and thereby target or destroy, any individual patient’s breast tumor because the cancer cells are constantly changing. Within each woman’s tumor, an evolution-like process is ongoing, leading to selection of treatment-resistant cells. This is not news in oncology; the concept has been understood for years as it applies to “liquid” tumors like leukemia, as he points out.

In breast cancer, understanding the complexity of each case is more recent. Gorski considers a genetic analysis of 104 triple negative breast cancer (TNBC) cases presented at the recent AACR meeting and published last week in Nature:

“…The 59 scientists involved in this study expected to see similar gene profiles when they mapped on computer the genomes of 100 tumours.

But to their amazement they found no two genomes were similar, never mind the same. “Seeing these tumours at a molecular level has taught us we’re dealing with a continuum of different types of breast cancer here, not just one,” explains Steven Jones, co-author of this study.

…TNBC is not a single disease. In fact, even an individual TNBC tumor is not a single disease. Tumor cells evolve as they proliferate, so that the cells in them are genetically heterogeneous. The cells growing in one area of a tumor can and often do harbor markedly different genetic mutations from the cells growing in another part of the tumor…

The team found that each tumor displayed multiple “clonal genotypes,” suggesting that the cancer would have to be treated as multiple diseases, rather than a single entity.

So besides that there are distinct subtypes of breast cancer, those labeled as TNBC are diverse and contain variation within; each patient harbors sub-clones of malignant cells that, in principle, respond differently to treatment.

Orac, the fictional supercomputer (Wiki-Commons image)

Putting these links together –

The message from Katherine O’Brien, who lives with MBC and blogs about it, is that one outlier – like Katherine Russell Rich – can provide hope to other patients and, maybe, clues for scientists about why she lived for so long with metastatic BC. The message from Orac, a physician-scientist blogger, is how hard it is to pinpoint an individual breast tumor’s molecular aspects, because the disease is so mutable and diverse.

The problem, and this reflects evolution in my thinking over a long while, is that published data – the gold standard, what supports EBM – are largely limited to findings based on trials of groups. We understand now, better than we did 10 or 20 years ago, that each patient’s tumor is unique and can evolve over time, naturally or in response to therapy. Clinical trials, though rigorously planned and elaborately structured, are incredibly expensive and flip-floppy, disappointing overall.

What I’m thinking –

Algorithms – except in the broadest sense – may not offer the optimal approach to cancer treatment. Maybe the median doesn’t matter so much as we’d thought.

Here’s a ~retro idea: In 2012, maybe the ideal and most cost-effective oncology practice would blend low-tech observations – like findings on physical examination and how the patient’s feeling – with occasional, high-tech analyses – like markers for genetic drift within a tumor. If doctors are well-trained and non-robotic, in either the literal or figurative sense, and if they lack COIs regarding treatment decisions, they’d provide better, more effective and personalized treatments than what’s typically offered based on evidence reached through elaborate, costly clinical trials of many patients with similar but non-identical cancers.

2. The researchers use mathematical arguments so complex to prove a point that Einstein would certainly, 100%, without a doubt, take issue with their model and proof.

3. “Overdiagnosis” is not defined in any clinical sense (such as the finding of a tumor in a woman that’s benign and doesn’t need treatment). Here, from the paper’s abstract:

The percentage of overdiagnosis was calculated by accounting for the expected decrease in incidence following cessation of screening after age 69 years (approach 1) and by comparing incidence in the current screening group with incidence among women 2 and 5 years older in the historical screening groups, accounting for average lead time (approach 2).

No joke: this is how “overdiagnosis” – the primary outcome of the study, is explained. After reading the paper in its entirety three times, I cannot find any better definition of overdiagnosis within the full text. Based on these manipulations, the researchers “find” an estimated rate of overdiagnosis attributable to mammography between 18 -25% by one method (model/approach 1) or 15-20% (model/approach 2).

4. The study includes a significant cohort of women between the ages of 70-79. Indolent tumors are more common in older women who, also, are more likely to die of other causes by virtue of their age. The analysis does not include women younger than 50 in its constructs.

5. My biggest concern is how this paper was broadcast – which, firstly, was too much.

Bloomberg News takes away this simple message in a headline: “Breast Cancer Screening May Overdiagnose by Up to 25%.” Or, from the Boston Globe’s Daily Dose, “Mammograms may overdiagnose up to 1 in 4 breast cancers, Harvard study finds.” (Did they all get the same memo?)

The Washington Post’s Checkup offers some details: “Through complicated calculations, the researchers determined that between 15 percent and 25 percent of those diagnoses fell into the category of overdiagnosis — the detection of tumors that would have done no harm had they gone undetected.” But then the Post blows it with this commentary, a few paragraphs down:

The problem is that nobody yet knows how to predict which cancers can be left untreated and which will prove fatal if untreated. So for now the only viable approach is to regard all breast cancers as potentially fatal and treat them with surgery, radiation, chemotherapy or a combination of approaches, none of them pleasant options…

This is simply not true. Any pathologist or oncologist or breast cancer surgeon worth his or her education could tell you that not all breast cancers are the same. There’s a spectrum of disease. Some cases warrant more treatment than others, and some merit distinct forms of treatment, like Herceptin, or estrogen modulators, surgery alone…Very few forms of invasive breast cancer warrant no treatment unless the patient is so old that she is likely to die first of another condition, or the patient prefers to die of the disease. When and if they do arise, slow-growing subtypes should be evident to any well-trained, modern pathologist.

“Mammograms Spot Cancers That May Not Be Dangerous,” said WebMD, yesterday. This is feel-good news, and largely wishful.

A dangerous message, IMO.

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Addendum, 4/15/12: The abstract of the Annals paper includes a definition of “overdiagnosis” that is absent in the body of the report: “…defined as the percentage of cases of cancer that would not have become clinically apparent in a woman’s lifetime without screening…” I acknowledge this is helpful, in understanding the study’s purpose. But this explanation does not clarify the study’s findings, which are abstract. The paper does not count or otherwise directly measure any clinical cases in which women’s tumors either didn’t grow or waned. It’s just a calculation. – ES

One advantage of blogging is that I can share my ideas, directly, with people who find them interesting, provocative or otherwise read-worthy. So for those who are curious, here is my general view on health care reform (HCR) by any name, in 3 points:

First, we need it. The U.S. health care system doesn’t work. It doesn’t serve doctors. Good physicians are few and far between in some geographical regions, in primary care and in needed specialties (like oncology and geriatrics). It doesn’t serve people who might be patients, except if they happen to work for a generous employer that offers a good plan (few do), they are rich enough so they might spend thousands each year out-of-pocket and out-of-network, or they are most fortunate of all, having no serious medical problems to contend with or pay for.

Second, although I wholeheartedly support the Affordable Care Act, because it’s a step in the right direction, I don’t think the legislation goes far enough. We need a simpler, single-payer solution, as in a national health care program, Medicare-style, for all. Why? Because the quasi-plan for state-based exchanges, each with competing offerings and not necessarily interpretable terms of coverage, is too complicated. There’s no reason to think a free market operating at the state level would match the public’s or many individuals’ medical needs. As long as each provider is trying to make a buck, or a billion, it won’t put patients’ access to good care first. Besides, there’ll be administrative costs embedded in each exchange that we could live better without. As for private insurers, well, I couldn’t care less about the well-being of those companies or their executives’ incomes.

Profit is not what medical care is about, or should be about. What we need is a simple, national health plan, Europe-style, available to everyone, with minimal paperwork and, yes, limits to care.

Third point – on rationing.

Some of my readers may wonder how I, who support some costly components of good medical care, like providing breast cancer screening for middle-aged women and sometimes giving expensive drugs to people with illness, favor health care reform. New cancer meds cost around $100,000 year, more or less, as do innovative treatments for cystic fibrosis, inflammatory bowel disease, rheumatoid arthritis and other conditions. I don’t think the sane solution is abandoning expensive but life-saving and quality-of-life-improving treatments.

The hardest part of this debate and what’s so rarely discussed is the appropriate limits of medical treatment, not based on costs – which we can certainly afford if we pull back on administrative expenses of health care and insurers’ huge profits – but on factors like prognosis and age. So, for example, maybe a 45 year old man should get a liver transplant ahead of an 80 year old man. Screening for breast cancer, if it is valuable as I think it is, should perhaps be limited to younger women, maybe those less than 70 or 75, based on the potential for life-years saved. Maybe we shouldn’t assign ICU beds to individuals who are over 85, or 95, or 100 years old.

The real issue in HCR, if you ask me, is who would decide on these kinds of questions. That conversation’s barely begun, and I would like to participate in that…

Meanwhile, the Supreme Court is busy doing its thing, sorting out whether the Affordable Care Act is constitutional or not. I’m glad they’re on the case, so that they might find that it stands and we can move on and forward.

Last week the Annals of Internal Medicine published a new report on how doctors (don’t) understand cancer screening stats. This unusual paper reveals that some primary care physicians – a majority of those who completed a survey – don’t really get the numbers on cancer incidence, 5-year survival and mortality.

The report shows, plainly and painfully, that too many doctors are confused and even ignorant of some statistical concepts. Nothing more, nothing less. The new findings have no bearing on whether or not cancer screening is cost-effective or life-saving.

What the study does suggest is that med school math requirements should be upped and rigorous, counter to the trend. And that we should do a better job educating students and reminding doctors about relevant concepts including lead-time bias, overdiagnosis and – as highlighted in two valuable blogs just yesterday, NPR Shots and Reporting on Health Antidote – the Number Needed to Treat, or NNT.

The Annals paper has yielded at least two unfortunate outcomes. One, which there’s no way to get around, is the clear admission of doctors’ confusion. In the long term, this may be a good thing, like admitting a medical error and then having QA improve as a consequence. But meanwhile some doctors at their office desks and lecterns don’t realize what they don’t know, and there’s no clear remedy in sight.

Dr. Moyer, in her editorial, writes that medical journal editors should carefully monitor reports to ensure that results aren’t likely misinterpreted. She says, in just one half-sentence, that medical educators should improve teaching on this topic. And then she directs the task of stats-ed to media and journalists, who, she advises, might follow the lead of the “watchdog” HealthNewsReview. I don’t see that as a solution, although I agree that journalists should know as much as possible about statistics and limits of data about which they report.

We lie, we cheat, we steal, we are confused… What else can doctors do wrong?

The second, and I think unnecessary, problematic outcome of this report is that it’s been used to argue against cancer screening. In the editorial Dr. Moyer indulges an ill-supported statement:

…several analyses have demonstrated that the vast majority of women with screen-detected breast cancer have not had their lives saved by screening, but rather have been diagnosed early with no change in outcome or have been overdiagnosed.

The problem of overdiagnosis, which comes up a lot in the paper, is over-emphasized, at least as it relates to breast cancer, colon cancer and some other tumors. I have never seen a case of vanishing invasive breast cancer. In younger women, low-grade invasive tumors are relatively rare. So overdiagnosis isn’t applicable in BC, at least for women who are not elderly.

In the second paragraph Dr. Moyer outlines, in an unusual mode for the Annals, a cabal-like screening lobby:

…powerful nonmedical forces may also lead to enthusiasm for screening, including financial interests from companies that make tests or testing equipment or sell products to treat the conditions diagnosed and more subtle financial pressures from the clinicians whose daily work is to diagnose or treat a condition. If fewer people are diagnosed with a disease, advocacy groups stand to lose contributions and academics who study the disease may lose funding. Politicians may wish to appear responsive to powerful special interests…

While she may be right, that there are some influential and self-serving interests and corporations who push aggressively, and maybe too aggressively for cancer screening, it may also be that some forms of cancer screening are indeed life-saving tools that should be valued by our society. I think, also, that she goes too far in insinuating that major advocacy groups push for screening because they stand to lose funding.

I’ve met many cancer agency workers, some founders, some full-time, paid and volunteer helpers – with varied priorities and goals – and I honestly believe that each and every one of those individuals hopes that the problem of cancer killing so many non-elderly individuals in our society will go away. It’s beyond reason to suggest there’s a hidden agenda at any of the major cancer agencies to “keep cancer going.” There are plenty of other worthy causes to which they might give their time and other resources, like education, to name one.

Which leads me back to the original paper, on doctors’ limited knowledge –

As I read the original paper the first time, I considered what would happen if you tested 412 practicing primary care physicians about hepatitis C screening, strains, and whether or not there’s a benefit to early detection and treatment of that common and sometimes pathologic virus, or about the use of aspirin in adults with high blood pressure and other risk factors for heart disease, or about the risks and benefits of drugs that lower cholesterol.

It seems highly unlikely that physicians’ uncertainty is limited to conceptual aspects of cancer screening stats. Knowing that, you’d have to wonder why the authors did this research, and why the editorial pushes so hard the message of over-screening.

Women’s health has never really been at the heart of ML. Your author has, historically, relegated subjects like normal menstruation, healthy pregnancy and reproduction and natural menopause to her gynecologist friends. Sure, I learned about the facts of life. I even studied them in med school and answered questions, some correctly, along the way. By now, I’ve lived through these real life-phases directly. But these topics never drew me. That’s changed now.

Women’s care – and lives, in effect – are jeopardized on three fronts:

First, on birth control. Last week the Senate narrowly tabled a move to limit insurers’ responsibility to cover contraception. The vote on the so-called “conscience” amendment was 51-48. What this tells us is that essentially half of that powerful group either agrees with limiting women’s access to birth control or sees it as dispensable in the context of political aims.

The very fact that the proposal reached the Senate floor is disturbing. Without access to birth control, women – including teenagers, people with significant medical problems that can be exacerbated by pregnancy, those who can’t afford to feed another child, and some who are already troubled or otherwise might not be ready or prepared to have children – are much more likely to become pregnant. It shouldn’t take a doctor to articulate this obvious point, and I can’t understand why so many are silent on it, but since so few physicians and the AMA in particular hasn’t issued any statement on this, I’ll stick my neck out and say it clearly: Lack of contraception puts women and their conceivable future-kids at risk for health problems that could be avoided.

The language surrounding the amendment is problematic, besides. Who are the anti-birth control legislation-writers to imply that “conscience” is involved in withholding contraception, and not the other way around? It’s like the “pro-lifers” who’ve implied that the rest of us aren’t.

Second, on access to safe abortions. I respect that some people think it’s wrong to terminate a pregnancy. But I also know that plenty of women, especially young women, get pregnant who don’t want to be pregnant. Regardless of who’s “responsible” – and any reader of this blog knows I’m no sucker for finger-pointing and behavior blame games – the bottom line is that if abortions become out-of-reach, women will suffer hemorrhage, life-threatening infections, permanent infertility and premature deaths.

Hard to know how many women had ill effects or died from botched abortions before January, 1973, when the Supreme Court issued its decision on Roe vs. Wade. Like most women of my generation, I know of those unfortunate outcomes only indirectly. Still, I can’t rid my brain of the scary, unclean place Natalie Wood visits with a wad of cash in the 1963 movie Love with the Proper Stranger, or the tragic outcome when actor Gael García Bernal takes his pregnant love to an abortionist in the film Crime of Padre Amaro, set a decade or so ago in Mexico. But the real scoop comes from older physicians and nurses, here and now. When I was in med school in the 1980s, they told me stories of women and girls showing up in the emergency room bleeding, pale… dead.

As outlined by editorialists and writers elsewhere, mergers of Catholic hospitals with other medical centers threaten to reduce or eliminate access to abortions in some rural areas. In states like Texas, the physical and emotional rigmarole to which pregnant women are subjected prior to an abortion – including mandatory listening to a description of the fetal organs and a discussion loaded make what might be a tough decision unbearable, especially if the woman lacks confidence.

Which leads me to the third point of vulnerability – that women should be able to obtain care without intimidation or emotional abuse.

When Rush Limbaugh spoke last week, he wasn’t just talking about one Georgetown Law student. He was speaking to and about millions of young women who are sexually active. He called them sluts and insinuated they are like prostitutes. Adding insult to verbal injury, he said he’d like to watch videos of the sex. You could say who cares, he’s just some right-winged showman blowing off steam and misogyny. But this is a man who speaks to conservative leaders and feeds ideas to many households in America. Scary that the Republican front-runners, men who would be President of the United States next year, didn’t call Rushbo out. Rather, they let it go. As they might your daughter’s health, or access to birth control, or to a safe abortion.

In this new climate of shame, it’s easy to imagine a girl in some communities might feel really, really bad about herself simply for being sexually active. Whether she’s 17 years in high school, or 21 years in college, or 25 and maybe a department store clerk – and possibly lonely or confused – she may be embarrassed to ask for birth control. The Scarlet C, Robert Walker aptly called it yesterday.

The paradox is that this kind of rough talk, posturing and in some states, puritanical law-making, make it more likely that a sexually active young woman will become pregnant. And if she does become so, now, she may delay seeing a doctor because she fears his or her moral judgment about her behavior. And that leads to less healthy outcomes, and more deaths – fetal and maternal.

This is a serious health issue. I wish more doctors would speak out about it.
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